Technical Field
The present disclosure relates to a method for preparing N-[[1-{3-(1,2,3-triazol-1-yl)propyl}piperidin-4-yl]methyl]-4-amino-5-chloro-2-methoxybenzamide, which is a benzamide derivative, or a pharmaceutically acceptable salt thereof; to an intermediate capable of being used in the preparation of the compounds; and to a method for preparing the intermediate.
Background Art
Serotonin (5-HT) is a neurotransmitter that is widely distributed throughout the body. Serotonin receptors have been known to 7 subtypes up to date, and there has been great interest in identifying 5-HT4 receptor, which is one of the 7 subtypes, and ascertaining pharmacological actions of 5-HT4 receptor. In general, 5-HT4 receptor agonist is found to be useful in treating various diseases such as gastroesophageal reflux disease, gastrointestinal disease, gastric motility disorder, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome (IBS), constipation, indigestion, esophagitis, gastroesophageal disease, motion sickness, central nervous system disease, Alzheimer's disease, cognitive disorder, emesis, migraine, neurological disease, pain, cardiovascular disorders, cardiac failure, cardiac arrhythmia, diabetes and apnea syndrome. (Tips, 1992, 13, 141; Ford A. P. D. W. et al., Med. Res. Rev., 1993, 13. 633; Gullikson G. W. et al., Drug Dev. Res., 1992, 26, 405; Richard M. Eglen et al., Tips, 1995, 16, 391; Bockaert J. et al., CNS Drugs, 1, 6; Romanelli M. N. et al., Arzheim Forsch./Drug Res., 1993, 43, 913; Kaumann A. et al., Naunyn-Schmiedeberg's. 1991, 344, 150; and Romanelli M, N. et al., Arzheim Forsch./Frug Res., 1993, 43, 913). Although 5-HT4 receptor agonist could be used extensively, barely any 5-HT4 receptor agonist compounds are being used in clinical stage. Therefore 5-HT4 receptor agonist that exhibits superior effects while having minimum side-effects has been required.
Benzamide derivatives have several superior pharmacological actions. Superior pharmacological actions of the benzamide derivatives are due to its action on nervous system that is controlled by serotonin, which is a neurotransmitter. The role of serotonin, that is pharmacological actions of benzamide derivatives, has been widely involved in various diseases for several years. Furthermore, researches have been focused on production and storage regions of serotonin as well as on defining relationship between location of serotonin receptor in human body and various disease statuses or diseases. Cisapride, that is a representative 5-HT4 receptor agonist, is one of benzamide derivatives. U.S. Pat. No. 4,962,115, U.S. Pat. No. 5,057,525 and U.S. Pat. No. 5,137,896 disclose N-(3-hydroxy-4-piperidinyl)benzamide comprising cisapride. These compounds are known to stimulate gastrointestinal motility. U.S. Pat. No. 5,864,039 and KR Patent No. 10-1180174 also disclose benzamide derivatives.
As explained above, the need for methods of economically and massively synthesizing benzamide derivatives having superior usability is increasing. Therefore, methods for preparing benzamide derivatives through fewer processing steps than conventional methods, which have improved yield and superior purity, are required.
The present inventors secured a method for preparing benzamide derivatives in high yield and purity wherein production of related compounds were markedly reduced compared to the conventional methods and the processing steps is minimized by using a novel intermediate, and completed the present disclosure upon confirmation of its applicability to a large-scale production.